Masonic Cancer Center, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN 55455, USA.
Lung Cancer. 2010 Jul;69(1):51-3. doi: 10.1016/j.lungcan.2009.09.008. Epub 2009 Oct 24.
The let-7 family of microRNAs are important regulatory molecules in lung cancer. One downstream target of let-7 is the RAS gene family, including KRAS, an important oncogene in the etiology and clinical outcome of lung adenocarcinoma. Recently, a SNP in the let-7 binding region of the KRAS 3' UTR was identified (termed LCS6). This functional polymorphism alters let-7 binding, resulting in both increased KRAS expression and decreased let-7 exposure. Further, this SNP has been reported as a risk trait for lung cancer among low-moderate smokers. Given the functionality of LCS6, we tested the hypothesis that this SNP is associated with the occurrence of KRAS mutation as well as patient survival. Here, we report there is no association between the LCS6 KRAS polymorphism and KRAS mutation. Further, we find no association between the LCS6 polymorphism and lung cancer survival. These unexpected findings imply that this newly reported KRAS-LCS6 polymorphism will have limited clinical utility for NSCLC.
miRNA 家族的 let-7 是肺癌中重要的调节分子。let-7 的一个下游靶标是 RAS 基因家族，包括 KRAS，这是肺腺癌发病机制和临床结果中的一个重要癌基因。最近，在 KRAS 3'UTR 的 let-7 结合区域发现了一个 SNP（称为 LCS6）。这种功能性多态性改变了 let-7 的结合，导致 KRAS 表达增加和 let-7 暴露减少。此外，该 SNP 已被报道为低-中度吸烟者肺癌的风险特征。鉴于 LCS6 的功能，我们检验了这样一个假设，即该 SNP 与 KRAS 突变的发生以及患者的生存有关。在这里，我们报告 LCS6 KRAS 多态性与 KRAS 突变之间没有关联。此外，我们发现 LCS6 多态性与肺癌的生存之间没有关联。这些意外的发现表明，这种新报道的 KRAS-LCS6 多态性在 NSCLC 中的临床应用将受到限制。
